Blame for README.md

---
license: other
tags:
  - single-cell
  - transcriptomics
  - foundation-model
  - circulating-tumor-cells
library_name: pytorch
---

# BioMod

BioMod is a single-cell transcriptomics foundation model built around gene modules
and an attention-based encoder. This repository provides pretrained model assets,
pretraining and fine-tuning code, and downstream task tutorials.

BioMod is released by **CTC-Atlas**, the joint laboratory of **Raymind Biotechnology
Co., Ltd** and the **Shenzhen Research Institute of Big Data (SRIBD)**.

[Installation](#installation) · [BioMod model weights](#biomod-model-weights) ·
[Tasks and examples](#tasks-and-examples) · [Usage notes](#usage-notes) ·
[Repository layout](#repository-layout)

## Installation

Download the project from [Hugging Face](https://huggingface.co/ctcatlas/BioMod).
Run the following commands from the parent of your intended project directory:

```bash
python -m pip install --upgrade huggingface_hub
hf auth login
hf download ctcatlas/BioMod --local-dir ./BioMod
cd BioMod
```

The download includes source code, model dependencies, the pretrained checkpoint,
and datasets. To omit datasets, add `--exclude "data/**"` to the download command.
If you already have the project, start from its root directory.

Create and activate the supplied Conda environment:

```bash
conda env create -f BioMod/environment.yml
conda activate biomod
```

The environment specification uses Python 3.9, PyTorch 2.6, CUDA 12.4, and PyTorch
Geometric 2.6. Conda creates the Python environment, then installs the pinned
GPU packages from the PyTorch/PyG wheel indexes through `requirements.txt`.
See [environment.yml](BioMod/environment.yml) and
[requirements.txt](BioMod/requirements.txt) for the complete dependency lists.
Match the GPU packages to your system when adapting the environment.

Pretraining uses CUDA/NCCL. The zero-shot
runner selects CUDA when available and otherwise uses CPU. Native Windows
execution has not been validated for the supplied environment.

To open a tutorial, choose its task directory. For cell annotation, run the
following from the outer repository root:

```bash
cd BioMod/cell_annotation
jupyter lab tutorial.ipynb
```

Use `drug_response`, `drug_combination`, `gene_perturbation`, or `zero_shot_batch`
in place of `cell_annotation` to open another task.

## BioMod model weights

This release includes the **BioMod model weights** and their matching
configuration. Use these files together; the configuration records the model
architecture and gene-module definitions.

| Asset | File |
| --- | --- |
| BioMod model weights | [BioMod.pth](weight/BioMod.pth) |
| Matching model configuration | [BioMod.pkl](weight/BioMod.pkl) |
| Model gene order | [selected_genes_27k.txt](model_dependencies/selected_genes_27k.txt) |
| Gene identifier mapping | [gene2ens.csv](model_dependencies/gene2ens.csv) |
| Gene2Vec embeddings | [selected_gene2vec_27k.npy](model_dependencies/selected_gene2vec_27k.npy) |
| Shared module definitions | [merged_biomods.json](model_dependencies/biomod_data_all/merged_biomods.json) |

The model components are bundled under
[`model_dependencies/pytorch_cont/`](model_dependencies/pytorch_cont/).
Legacy serialized names are handled by
[`biomod_compat.py`](model_dependencies/biomod_compat.py) when loading existing
checkpoints; the original checkpoint files remain unchanged.
Optional [Hallmark and Reactome source definitions](model_dependencies/biomod_data_sources/)
are kept in `biomod_data_sources/`. They are separate from the default checkpoint
runtime definitions in `biomod_data_all/`.
Task-specific checkpoint arguments are listed under
[Usage notes](#checkpoint-arguments).

## Tasks and examples

The following tasks have implementations in this repository. The links identify
available source code and examples; these workflows have not been validated end
to end with the bundled checkpoint.

| Task | Implementation | Notebook |
| --- | --- | --- |
| Cell-type annotation | [Fine-tuning script](BioMod/cell_annotation/train.py) | [Notebook](BioMod/cell_annotation/tutorial.ipynb) |
| Zero-shot cell embeddings and batch-effect evaluation | [Embedding and evaluation script](BioMod/zero_shot_batch/evaluate.py) | [Notebook](BioMod/zero_shot_batch/tutorial.ipynb) |
| Single-drug response regression (IC50) | [Training script](BioMod/drug_response/train.py) | [Notebook](BioMod/drug_response/tutorial.ipynb) |
| Drug-pair synergy classification | [Training script](BioMod/drug_combination/train.py) | [Notebook](BioMod/drug_combination/tutorial.ipynb) |
| Gene perturbation response prediction | [Training script](BioMod/gene_perturbation/train.py) | [Notebook](BioMod/gene_perturbation/tutorial.ipynb) |

### Commands by dataset

Each row below links to a separate, complete launch command for that task and
dataset or condition. Commands specify the input paths and output directory;
you do not need to adapt a command from another dataset. Run them in Bash from
the outer repository root after activating the environment. Read any
dataset-specific input caveats before launching.

| Task | Dataset or condition | Launch command |
| --- | --- | --- |
| Cell annotation | Kim Lung | [Complete command](BioMod/cell_annotation/README.md#1-kim-lung) |
| Cell annotation | Immune | [Complete command](BioMod/cell_annotation/README.md#2-immune) |
| Cell annotation | Liver | [Complete command](BioMod/cell_annotation/README.md#3-liver) |
| Cell annotation | MS (paired train/test files) | [Complete command](BioMod/cell_annotation/README.md#4-ms) |
| Cell annotation | hPancreas (hp14 paired files) | [Complete command](BioMod/cell_annotation/README.md#5-hpancreas) |
| Cell annotation | Zheng68K | [Complete command](BioMod/cell_annotation/README.md#6-zheng68k) |
| Cell annotation | Myeloid (reference/query files) | [Complete command](BioMod/cell_annotation/README.md#7-myeloid) |
| Zero-shot evaluation | hPNC | [Complete command](BioMod/zero_shot_batch/README.md#1-hpnc) |
| Zero-shot evaluation | BMMC | [Complete command](BioMod/zero_shot_batch/README.md#2-bmmc) |
| Zero-shot evaluation | Kim Lung: malignant cells retained | [Complete command](BioMod/zero_shot_batch/README.md#3-kim-lung-malignant-cells-retained) |
| Zero-shot evaluation | Kim Lung: malignant cells removed | [Complete command](BioMod/zero_shot_batch/README.md#4-kim-lung-malignant-cells-removed) |
| Single-drug response | GDSC-CCLE joint inputs | [Complete command](BioMod/drug_response/README.md#run-the-bundled-gdsc-ccle-collection) |
| Drug-combination synergy | Bundled training and validation collection | [Complete command](BioMod/drug_combination/README.md#run-the-bundled-training-and-validation-collection) |
| Gene perturbation | Norman | [Complete command](BioMod/gene_perturbation/README.md#2-run-the-bundled-norman-simulation-split) |

Paired training/test files and complementary drug/cell inputs belong to one
run configuration. Historical reference copies do not add datasets. The
[optional drug-combination cross-validation command](BioMod/drug_combination/README.md#optional-five-fold-cross-validation-on-the-same-collection)
uses the same collection under a different validation protocol.

### Pretraining

The repository also supports pretraining and continued pretraining.

| Workflow | Implementation | Documentation |
| --- | --- | --- |
| Pretraining and continued pretraining | [Pretraining script](BioMod/biomod.py) | [Source guide](BioMod/README.md), [launcher reference](BioMod/command.txt) |

Bundled input defaults resolve from each script's location. Command examples
state their working directory; explicit relative command-line paths are resolved
from that directory. Pretraining corpora, legacy reference checkpoints, and
generated analysis results must be supplied separately where indicated.

## Usage notes

### Project paths and notebooks

The project root contains `BioMod/`, `model_dependencies/`, `weight/`, and
`data/`. The inner `BioMod/` directory contains the source code. Task commands
may assume different working directories; adjust relative paths when following
a guide.

Each task keeps its notebook in `BioMod/<task>/tutorial.ipynb`. Start Jupyter
from the selected task directory, as shown in [Installation](#installation).
Each notebook sets `PROJECT_ROOT = Path('../..').resolve()` and derives absolute
runtime paths from the outer repository root. If the notebook kernel uses a
different working directory, set `PROJECT_ROOT` to the outer repository root
explicitly before running the path checks. Review the configuration cells before running:

| Setting | Location |
| --- | --- |
| `PROJECT_ROOT` | Outer project root containing `BioMod/`, `model_dependencies/`, `weight/`, and `data/` |
| `SOURCE_DIR` | `PROJECT_ROOT / 'BioMod'` |
| Asset or dependency directory | `PROJECT_ROOT / 'model_dependencies'` |
| Weight and configuration paths | The BioMod model weights and matching configuration listed above |
| `MODULE_DATA_DIR` | `model_dependencies/biomod_data_all/` under the project root |
| Data and output paths | Your task inputs and a writable output directory |

Checkpoint variable names differ by notebook: `CKPT_PATH` / `CONFIG_PKL`
for cell annotation, drug response, and zero-shot integration;
`SCFM_CKPT` / `SCFM_HYPER` for gene perturbation; and
`CHECKPOINT_PATH` / `HYPER_PARAMS_PATH` for drug combination.
Training defaults to disabled (`RUN_TRAINING = False`). The zero-shot notebook
uses `RUN_EVALUATION = False` and enables UMAP export separately with `MAKE_UMAP`.
Output directories are created when the corresponding operation is enabled.

### Checkpoint arguments

| Task | Weights argument | Configuration argument |
| --- | --- | --- |
| Drug response / drug combination | `--checkpoint_path` | `--hyper_params_path` |
| Zero-shot / gene perturbation | `--scfm_ckpt_path` | `--scfm_hyper_params_path` |
| Cell annotation | `--biomod_checkpoint` | `--config_pkl` |
| Continued pretraining | `--model_path` | `--model_config_path` or paired-file discovery |

### Data and evaluation

Datasets are stored under `data/`. Input formats, metadata fields, preprocessing,
and train/validation splits depend on the task; follow the linked implementation
and tutorial.

For zero-shot embeddings, provide an h5ad expression matrix and specify the gene,
batch, and cell-type metadata fields. The runner aligns genes to the model gene
list and fills missing genes with zeros. It does not normalize or log-transform
the input matrix, so prepare expression values according to the intended protocol.
Resolve duplicate gene identifiers and inspect gene overlap before evaluating
embeddings.

The drug-response and drug-combination workflows use validation metrics for
checkpoint selection. Their validation results should not be presented as
performance on an independent final test set.

## Repository layout

The tree below includes source files, model dependencies, and the pretrained
checkpoint. The top-level `data/` and `.cache/` directories are omitted for
readability. Folder descriptions explain where to find each component.

<details>
<summary>Expand the full repository structure</summary>

```text
BioMod/                                                        # Project root: source code, model dependencies and weights
├── BioMod/                                                    # Task code: training, evaluation and tutorials
│   ├── cell_annotation/                                       # Cell-type annotation and model fine-tuning
│   │   ├── README.md
│   │   ├── train.py
│   │   └── tutorial.ipynb
│   ├── drug_combination/                                      # Drug-combination synergy prediction
│   │   ├── README.md
│   │   ├── train.py
│   │   └── tutorial.ipynb
│   ├── drug_response/                                         # Single-drug response prediction
│   │   ├── README.md
│   │   ├── train.py
│   │   └── tutorial.ipynb
│   ├── gene_perturbation/                                     # Gene perturbation response prediction
│   │   ├── components/                                        # Task models, datasets, training and inference helpers
│   │   │   ├── __init__.py
│   │   │   ├── data_utils.py
│   │   │   ├── dataset.py
│   │   │   ├── inference.py
│   │   │   ├── model.py
│   │   │   ├── trainer.py
│   │   │   ├── training_utils.py
│   │   │   └── utils.py
│   │   ├── README.md
│   │   ├── train.py
│   │   └── tutorial.ipynb
│   ├── zero_shot_batch/                                       # Zero-shot integration and evaluation
│   │   ├── tools/                                             # Optional visualization and evaluation tools
│   │   │   ├── sequencing_depth/                              # Low-depth expression generation and evaluation
│   │   │   │   ├── make_low_depth_h5ad.py
│   │   │   │   ├── README.md
│   │   │   │   └── run_zero_shot_low_depth.py
│   │   │   └── visualize_results.py
│   │   ├── evaluate.py
│   │   ├── README.md
│   │   └── tutorial.ipynb
│   ├── .gitattributes
│   ├── .gitignore
│   ├── biomod.py
│   ├── biomod_dataset.py
│   ├── command.txt
│   ├── environment.yml
│   ├── models_biomod.py
│   ├── README.md
│   ├── requirements.txt
│   └── training_utils.py
├── model_dependencies/                                        # Shared gene mappings, embeddings and model components
│   ├── biomod_data_all/                                       # Default merged module definitions and construction tools
│   │   ├── create_uncovered_biomods.py
│   │   ├── merge_biomods.py
│   │   └── merged_biomods.json
│   ├── biomod_data_sources/                                   # Optional source gene sets and their loading helper
│   │   ├── biomod1_hallmarks.json
│   │   ├── biomod2_reactome_2022_filtered.json
│   │   └── load_biomod.py
│   ├── pytorch_cont/                                          # Attention and model components
│   │   ├── __init__.py
│   │   ├── ding_models.py
│   │   ├── pytorch.py
│   │   ├── pytorch_old.py
│   │   └── reversible.py
│   ├── biomod_compat.py                                      # Legacy checkpoint and configuration compatibility
│   ├── gene2ens.csv
│   ├── selected_gene2vec_27k.npy
│   └── selected_genes_27k.txt
├── weight/                                                    # Pretrained weights and matching model configuration
│   ├── BioMod.pkl
│   └── BioMod.pth
├── .gitattributes
├── .gitignore
└── README.md
```

</details>

## Partners

- [Raymind Biotechnology Co., Ltd](https://en.raymind.com/)
- [Shenzhen Research Institute of Big Data (SRIBD)](https://www.sribd.cn/en)